Figure 6.

Four multi-organ systems used to demonstrate organ-organ interaction and toxicity to compounds using functional readouts obtained via integrated on-chip sensors. (A) Schematic overview of the microfluidic device and on-chip sensors used by Oleaga et al (2018) to demonstrate real time changes to off target cardiotoxicity due to hepatic metabolism. (organ-organ interaction). The sensors used include silicon cantilevers for cardiac force, microelectrode array for cardiac electrophysiological data. Reprinted from Biomaterials 182: 176–190, vol 182, Carlota Oleaga, Anne Riu, Sandra Rothemund, Andrea Lavado, Christopher W. McAleer, Christopher J. Long, Keisha Persaud, Narasimhan Sriram Narasimhan, My Tran, Jeffry Roles, Carlos A. Carmona-Moran, Trevor Sasserath, Daniel H. Elbrecht, Lee Kumanchik, L. Richard Bridges, Candace Martin, Mark T. Schnepper, Gail Ekman, Max Jackson, Ying I. Wang, Reine Note, Jessica Langer, Silvia Teissier, James J. Hickman, Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system (ref 23). Copyright 2018, with permission from Elsevier. (B) Schematic overview of system and on chip sensors used by Zhang et al (2017) to demonstrate real time drug toxicity in a heart-liver system.¹⁵ An integrated biochemical sensor module was used to measure biomarkers of interest pointing to toxicity. Reproduced from Zhang, Y. S.; Aleman, J.; Shin, S. R.; Kilic, T.; Kim, D.; Mousavi Shaegh, S. A.; Massa, S.; Riahi, R.; Chae, S.; Hu, N.; Avci, H.; Zhang, W.; Silvestri, A.; Sanati Nezhad, A.; Manbohi, A.; De Ferrari, F.; Polini, A.; Calzone, G.; Shaikh, N.; Alerasool, P., et al. Proc Natl Acad Sci U S A 2017, 114, E2293-E2302 (ref 15), with permission from proceedings of the national academy of sciences USA. (C) Schematic overview of a microfluidic system with integrated microelectrode arrays and TEER electrodes to demonstrate the effect of TNF-alpha on vascular endothelium and cardiomyocytes. Reproduced from Maoz, B. M., A. Herland, O. Y. F. Henry, W. D. Leineweber, M. Yadid, J. Doyle, R. Mannix, V. J. Kujala, E. A. FitzGerald, K. K. Parker and D. E. Ingber, Lab Chip 17(13): 2294–2302 (ref 49), with permission of The Royal Society of Chemistry. (D) Schematic overview of multiorgan microfluidic set up with integrated TEER electrodes and optical monitoring of cardiac beating in a heart-liver-lung system.¹⁷ Reproduced under the terms of the CC-BY-4.0 license. Copyright 2017, the authors.